Pressure-mediated mechanosensitive Piezo2 channel promotes bladder fibrosis in patient with neurogenic bladder

Lv L1, Wen J2, Zhang Y3, Li Q3, Wang J4, Wen Y1, Wang Q5

Research Type

Pure and Applied Science / Translational

Abstract Category

Neurourology

Best Non-Clinical Abstract
Abstract 325
Science 4 - Neurourology
Scientific Podium Short Oral Session 28
Saturday 20th September 2025
16:00 - 16:07
Parallel Hall 2
Spinal Cord Injury Pediatrics Pathophysiology Sensory Dysfunction Underactive Bladder
1. Department of Urology and Henan Joint International Paediatric Urodynamic Laboratory, First Affiliated Hospital of Zhengzhou University, 2. Pediatric Urodynamic Center, Department of Urology and Henan Joint International Paediatric Urodynamic Laboratory, First Affiliated Hospital of Zhengzhou University, 3. Pediatric Urodynamic Center,Department of Urology and Henan Joint International Paediatric Urodynamic Laboratory, First Affiliated Hospital of Zhengzhou University, 4. Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, 5. Department of Urology of First Affiliated Hospital of Zhengzhou University, China
Presenter
Links

Abstract

Hypothesis / aims of study
Bladder fibrosis seriously affects the quality of life and upper urinary tract safety of patients with neurogenic bladder, and its mechanism is still not fully understood. Mechanosensitive Piezo2 channels have been found to play an important role in bladder pressure perception in recent years, but its role in neurogenic bladder has not been reported. This is an original research to explore the change of Piezo2 in neurogenic bladder and its role in bladder fibrosis in both human beings and  animals.
Study design, materials and methods
Bladder tissues from children with neurogenic bladder who underwent ileocystoplasty (n=6, aged 10.50±4.76 years) and well-matched normal bladder tissues from patients with ureteral reimplantation surgery (n=6, aged 11.67±2.80 years) were collected to detect changes in Piezo2 and fibrosis indicators. An animal model of neurogenic bladder was established by transecting the L6 and S1 spinal nerves of juvenile Sprague-Dawley rats. Cystometry were performed on rats at 2, 6, and 12 weeks, and bladders were collected to examine Piezo2, epithelial-mesenchymal transition (EMT), and fibrosis indicators. Transcriptome sequencing was performed on the sham group and 2-week neurogenic bladder group rats. The effect of pressure on fibrosis was investigated by stretching human bladder epithelial cells (SV-HUC-1) in vitro, and the role of Piezo2 in this process was explored by adding Piezo2 siRNA.
Results
The results of Westing blot showed the expression of Piezo2 was significantly increased in human NB bladder and positively correlated with the bladder pressure (R2=0.8375, P=0.0105) and degree of fibrosis (R2=0.9603, P=0.0006) (Figure 1AB). With the time prolonged, bladder fibrosis gradually worsened in NB rat model. Cystometry showed that bladder pressure increased significantly at 2 weeks, and decreased slightly at 6 and 12 weeks, but was still higher than that of the control group (Figure 1C). In addition, the bladder of the NB rat model showed a significant increase in Piezo2 at 2 weeks, and was significantly higher than the control group at 6 and 12 weeks (Figure 1D). RNA-seq analysis showed that in bladder fibrosis caused by spinal cord injury (SCI), responses to mechanical stimulation, detection of mechanical stimulation related to pain perception, collagen-containing extracellular matrix and calcium signaling pathways were activated. In SV-HUC-1 cells, stretching led to significant fibrosis, while Piezo2 siRNA could alleviate fibrosis. EMT plays an important role in the above process (Figure 2).
Interpretation of results
Piezo2 expression was significantly increased in human NB bladder, correlating with bladder pressure and fibrosis severity. Fibrosis progressively worsened over time, with increased bladder pressure peaking at 2 weeks and remaining elevated at 12 weeks in the NB rat model. At the same time Piezo2 levels were significantly higher at 2 weeks and remained elevated. RNA-seq showed activation of mechanical stimulation, pain perception, extracellular matrix, and calcium signaling pathways in SCI-induced bladder fibrosis. In SV-HUC-1 cells, stretching-induced fibrosis was reduced by Piezo2 siRNA, with EMT playing a key role. This suggests that PIezo2 is highly expressed in SCI-induced neurogenic bladder and promotes bladder fibrosis progression via EMT, which will help develop drugs to alleviate fibrosis.
Concluding message
Mechanosensitive Piezo2 channels sense pressure changes in neurogenic bladder and promote bladder fibrosis progression through EMT. Stretching SV-HUC-1 cells in vitro can promote fibrosis, and inhibiting Piezo2 channels can alleviate this process.
Figure 1 Figure 1. Piezo2 expression in human and NB rat models
Figure 2 Figure 2. Inhibition of Piezo2 alleviates cell stretch-induced fibrosis of bladder epithelial cells
Disclosures
Funding National Natural Science Foundation of China(82470807) Clinical Trial No Subjects Human Ethics Committee Ethics Committee of the First Affiliated Hospital of Zhengzhou University Helsinki Yes Informed Consent Yes
07/07/2025 12:37:06